Hair loss due to flea control products

Evaluation of hair loss in cats occurring after treatment with a topical flea control product.

Credille KM,et al Eli Lilly and Company

Abstract

BACKGROUND:
A formulation containing 39.6% spinetoram resulted in a higher than anticipated number of reports of alopecia at the site of application in the first months following commercial product launch.

HYPOTHESIS/OBJECTIVES:

To determine the cause of the alopecia using histopathology, including assessment for inflammation, follicular findings of physical trauma (plucking/pulling behaviour) and changes in follicular cycling.

ANIMALS:

Twenty-four flea-free, male and female adult domestic short hair cats within a private research colony.

METHODS:

Cats were treated with a single application of 39.6% spinetoram on day 0; personnel were not blinded. Observations of the skin and hair coat began immediately and were repeated at 30 min and 1, 2, 3, 4, 6, 8 and 12 h post-application and then on subsequent days at the same time as initial dosing and at 2, 4, 6, 8 and 12 h after that time, until day 5. If hair thinning or loss was observed, a skin biopsy sample was collected. Two cats not exhibiting abnormalities were biopsied on day 6.

RESULTS:

Thirty-eight per cent of cats (nine of 24) developed hair thinning and alopecia of sufficient severity within 78 h post-application of the product to warrant skin biopsy. Abnormalities in the skin were limited to the application site and were consistent with physical trauma (pulling or plucking) to the hair.

CONCLUSIONS AND CLINICAL IMPORTANCE:

Microscopic changes in the hair follicles of affected cats were consistent with self-induced trauma or barbering behaviour. All changes were reversible and paralleled findings associated with well-established, topical flea control products.

Role of 5¨»-reductase inhibitors in androgen-stimulated skin disorders.

Azzouni F, et al

Abstract

5¦Á-reductase (5¦Á-R) isozymes are ubiquitously expressed in human tissues. This enzyme family is composed of 3 members that perform several important biologic functions. 5¦Á-R isozymes play an important role in benign prostate hyperplasia, prostate cancer, and androgen-stimulated skin disorders, which include androgenic alopecia or male pattern hai rloss, acne, and hirsutism. Discovery of 5¦Á-R type 2 deficiency in 1974 sparked interest in development of pharmaceutical agents to inhibit 5¦Á-R isozymes, and 2 such inhibitors are currently available for clinical use: finasteride and dutasteride. 5¦Á-R inhibitors are US Food and Drug Administration (FDA)-approved for the treatment of benign prostate hyperplasia. Only finasteride is FDA-approved for treatment of male patter hair loss. This article reviews the pathophysiology of androgen-stimulated skin disorders and the key clinical trials using 5¦Á-R inhibitors in the treatment of androgen-stimulated skin disorders. J Drugs Dermatol. 2013;12(2):e30-e35.

BACKGROUND: Androgenetic alopecia is the most common form of hair loss. It is a clinical entity of relevant interest and presents a significant psychosocial impact as it undermines self-esteem and quality of life in female patients due to the importance of the hair for people's facial balance.

OBJECTIVE: The purpose of the present study is to evaluate dermoscopic signs in women clinically diagnosed with androgenetic alopecia.

METHOD: Observational study with 34 women between 17 and 68 years old who were diagnosed with androgenetic alopecia. All of them underwent photographic sessions with a 10x magnification dermoscope and a digital camera zoom set to 20x magnification and 40x magnification on the scalp frontal midline.

RESULTS: All patients showed miniaturization. A peripilar brown halo was found in 22 patients, honeycomb-like scalp pigmentation was found in 14 and yellow dots in only 1 patient. Recent studies show dermoscopy as the new tool for diagnosis assistance and treatment follow up in scalp disorders. Our study used an ordinary dermoscope and we evaluated several findings reported in the literature with significant clarity and easiness.

CONCLUSION: The dermoscope, which is used by dermatologists on a daily basis, is an excellent tool to assist in early diagnosis and assessment of therapeutic response in androgenetic alopecia.

Transplanting between existing hair grafts

A technique for hair-grafting in between existing follicles in patients with early pattern baldness. Brandy DA.

BACKGROUND: When using follicular hair transplantation for hair loss on patients with early male or female pattern baldness, there can be significant trauma to preexisting hair follicles. This becomes especially important in view of the fact that finastride and minoxidil can stop or slow hair loss. OBJECTIVE: To develop a system that averts damage to preexisting hair follicles in patients with early male or female pattern baldness. METHODS: A Lutex headlight (2.5-3.5x loupe magnification system) is used to make 1.0-1.5 mm spear incisions in between the hair follicles in patients with early male or female pattern balding. Magnification is also utilized during the graft cutting and placement phases of the operation. RESULTS: This headlight-loupe magnification system has dramatically decreased the amount of permanent hair loss and anagen effluvium on 144 patients with early male and female pattern hair loss. With less permanent hair loss there is greater density observed with each progressive session. CONCLUSION: Hair transplant surgeons now have a method to consistently and significantly minimize the amount of damage to preexisting hair follicles in patients in the early stages of male and female pattern baldness. This becomes even more important in light of the fact that more and more patients are using finastride or minoxidil to stop the thinning process. Existing hairs can therefore be preserved.

Background Topical immunotherapy has recently been found useful in the treatment of chronic and extensive Alopecia Areata (AA). Objective To evaluate the efficacy and safety of diphenylcyclopropenone (DPCP) use among Chinese patients with steroid resistant and extensive AA in our institute. Methods The medical records of 31 Chinese patients treated with DPCP were analysed retrospectively. The efficacy, adverse effects, and relapse rate of DPCP treatment were reviewed. Results Thirty-one (16 male, 15 female) Chinese patients with extensive, steroid resistant Alopecia Areata and a mean age of 28.9 years (SE 10.4) were treated. The mean age of onset was 17.8 years (SE 8.8) with an average disease duration of 11.2 years (SE 7.7). Ten patients had a history of atopy and 4 had a history of thyroid disease. Nail changes were found in 14 patients and a family history of AA was found in 2 patients. Thirteen patients (41.9%) had experienced total hair loss. Two patients abandoned the treatment due to severe side effects. Of the remaining 29 patients, 4 (13.8%), 7 (24.1%), 5 (17.2%), and 13 (44.8%) achieved >90% complete response, >50-90% partial response, >10-50% minimal response, and <10% no response hair regrowth, respectively. Adverse effects included pruritus, erythema, vesiculation, scaling, cervical lymphadenopathy, dyspigmentation and urticarial reactions. Relapse occurred (>25% hair loss) in 69.23% of patients after 18 months of follow up. Conclusions DPCP is an effective and tolerable treatment for Chinese patients with extensive, steroid resistant AA.

A robot for follicular unit extraction

Follicular Unit Extraction (FUE) has become a popular hair transplanting method for treating hair loss in male-pattern baldness. Manually harvesting hairs one by one, however, is a tedious and time-consuming job to doctors. We design an accurate hair harvesting robot with a novel and efficient end-effector which consists of one digital microscope and a punch device. The microscope is first employed to automatically localize target hairs and then guides the punch device for harvesting after shifting. The end-effector shows average bias and precision of 0.014 mm by virtue of a rotary guidance design for the motorized shifting mechanism.

Prevention of chemotherapy-induced hair loss

Hair loss is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects.- To prevent hair loss scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands.- The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs.- In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced hair loss.

Disease characteristics. Waardenburg syndrome type I (WS1) is an auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin, along with dystopia canthorum (lateral displacement of the inner canthi). The hearing loss in WS1 observed in approximately 60% of affected individuals is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. Most commonly, hearing loss in WS1 is bilateral and profound (>100 d. The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs.

Diagnosis/testing. The diagnosis of WS1 is established by clinical findings in most individuals: sensorineural hearing loss, pigmentary changes in the hair and eyes, and dystopia canthorum identified by calculation of the W index. PAX3 is the only gene known to be associated with WS1; molecular genetic testing by sequencing and deletion/duplication analysis of the PAX3 gene detects more than 90% of disease-causing mutations. Such testing is available clinically.

Management. Treatment of manifestations: Management of the hearing loss depends on its severity.

Testing of relatives at risk: If the family-specific PAX3 mutation is known, molecular genetic testing of relatives at risk allows for early screening of those at risk for hearing loss.

Other: Folic acid supplementation in pregnancy is recommended for women at increased risk of having a child with WS1 because of possibly increased risk of neural tube defects in association with WS1.

Genetic counseling. Waardenburg syndrome type I (WS1) is inherited in an autosomal dominant manner. The majority of probands have an affected parent. A minority of probands do not have an affected parent and are presumed to have a de novo mutation. Offspring of an individual with WS1 have a 50% chance of inheriting the disease-causing mutation. Prenatal testing is possible for pregnancies at increased risk if the PAX3 mutation in the family is known.

Diagnosis
Clinical Diagnosis
Diagnostic criteria for Waardenburg syndrome type I (WS1) have been proposed by the Waardenburg Consortium [Farrer et al 1992]. An individual must have two major criteria or one major plus two minor criteria to be considered affected.

Major Criteria
•Congenital sensorineural hearing loss

•White forelock, hair hypopigmentation

•Pigmentation abnormality of the iris:

◦Complete heterochromia iridum (irides of different color)

◦Partial/segmental heterochromia (two different colors in same iris, typically brown and blue)

An abnormal W index result is greater than 1.95. Previously, a W index of greater than 2.07 was necessary to diagnose WS1 in an individual meeting all of the other diagnostic criteria. With molecular analysis, a family previously classified clinically as having WS2 based on the W index was found to have a PAX3 mutation and was reclassified as having WS1 [Tassabehji et al 1993]. Hence, the W index threshold was reduced to its current value of greater than 1.95.

A new treatment for hair loss

Hair loss is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of Hair loss, which affects millions of men and women worldwide, and is an androgen driven disorder. Here, the Citrullus colocynthis Schrad fruit is evaluated for hair regrowth activity in androgen-induced alopecia. Petroleum ether extract of C. colocynthis was applied topically for its hair regrowth-promoting activity. Alopecia was induced in albino mice by testosterone administration intramuscularly for 21 days. Its inhibition by simultaneous administration of extract was evaluated using follicular density, anagen/telogen (A/T) ratio and microscopic observation of skin sections. Finasteride (5alpha-reductase inhibitor) solution was applied topically and served as positive control. Petroleum ether extract of C. colocynthis exhibited promising hair growth-promoting activity, as reflected from follicular density, A/T ratio and skin sections. The treatment was also successful in bringing a greater number of hair follicles in anagenic phase than the standard finasteride. The result of treatment with 2 and 5% petroleum ether extracts were comparable to the positive control finasteride. The petroleum ether extract of C. colocynthis and its isolate is useful in the treatment of androgen-induced alopecia.

Alopecia areata treated with topical minoxidil

A minoxidil topical solution was used to treat 48 patients with hair loss due to alopecia areata, ie, 24 patients with patchy disease and 24 patients with total hair loss or alopecia universalis. Twenty-five patients had terminal hair regrowth"; in 11 of the 25 patients, it was cosmetically acceptable. No clinical features of the disease seemed to indicate the likelihood of hair regrowth. Hair regrowth began two months after start of treatment and was not uniformly well maintained after the treatment was terminated. One patient had an allergic contact dermatitis reaction to the minoxidil solution; no systemic side effects were seen. No notable systemic absorption was found in 18 adult patients. Effects on cutaneous blood flow or the immune system or some direct effect on hair follicles are possible mechanisms by which minoxidil therapy might stimulate hair regrowth.

Caspases and hair regrowth

...Studies demonstrate that loss of hair follicles involves distinct patterns of expression of active caspases. Active caspase 8, an initiator of the death receptor pathway, was predominately found in the isthmic and upper lower portion of the shaft. This pattern of expression suggests that the death receptor pathway is activated during hair regrowth and is initiated by toxic substances that bind to death receptors, i.e., TNF-alpha. Interestingly, activated caspase 3, a downstream effector caspase, was higher in catagen hair then in other phases of the hair cycle, indicating a role in the terminal stage of the apoptotic pathway. Activated caspase 1 was also found in the hair bulb and hair shaft. This study suggests an important role of the infundibular area of the hair shaft where inner and outer root sheath are abruptly changing and that this area may play a role in the regulation of normal hair apoptosis. Caspase 3 seems to be playing the key role in the apoptotic pathway during the catagen phase of the hair cycle in these areas. Finasteride may exhibit its influence by selectively inhibiting DHT, which affects a multitude of "androgen responsive genes", such as the caspase pathway, which affects programmed cell death in the hair regrwothcycle

Uric acid and Stroke-- Dr Proctor's comments

This is Dr Proctor's paper on the relationship between uric acid and stroke. The same processes modulating hair loss also likely figure in stroke. Similarly, many agents that are effective in hair loss treatment are also effective in experimental models of stroke.